The goal of this application is to bring an Applied Biosystems 4000 QTrap hybrid tandem mass spectrometer with nano-LC to the Proteomics Core at Wayne State University. This instrument has unique capabilities for discovery of post translational modifications using the triple quadrupole capabilities and to accumulate identified ions in the linear ion trap component of the instrument for maximal sensitivity. The combined capabilities make the 4000 QTrap an exceptional instrument for both discovery and quantitation. The availability of the 4000 QTrap and a trained operator within the Proteomics Core will be a major asset to research programs of NIH-funded investigators at WSU. The instrument will address two critical needs that are currently not adequately met. The first of these is for the discovery of novel sites of post translational modification in proteins. The second is quantitation of proteins and modified proteins from very small samples. The only currently available MS/MS instrument at Wayne State University or in the metropolitan Detroit area that can be used for proteomic analysis is the LTQ-XL with ETD that is operated by the same Proteomics Core seeking to add the 4000QTrap. The LTQ is heavily used and does not have the capabilities to perform full spectrum neutral loss scans and is not the instrument of choice for mass tag based quantitation or multiple reaction monitoring. The Proteomics Facility Core within the EHS Center at WSU has been established as the only source for proteomic services at Wayne State. The University is strongly committed to this application as evidenced by the following support: 1) A long term plan for maintenance and operation of the Q Trap 4000. 2) Renovated laboratory space for the Proteomics Core Facility. 3) Funding for salary and training of a technician to operate and schedule usage of the instrument. The 4000 QTrap hybrid tandem mass spectrometer is a state-of-the-art system with unparalleled ability to detect and localize post-translational modifications in proteins and to perform both relative and absolute quantitation of peptides. At WSU, this instrument will allow more productive use of instrumentation already in place for proteomic fractionation and will provide efficient access to modern proteomic analysis for NIH- funded investigators. PUBLIC HEALTH RELEVANCE: Our cells, organs and systems are regulated by reversible changes in proteins such as phosphorylation, oxidation and the attachment of lipids or sugars. Understanding disease processes and validating medical therapies requires us to discover and measure the proteins and the changes in proteins. The 4000 QTrap efficiently searches for protein modifications and allows sensitive quantitation of proteins and modified proteins.